To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 controls) from the discovery set on the basis of principal component analysis; the follow-up stages included two independent sample sets (1,824 cases and 3,808 controls for follow-up 1 and 2,343 cases and 3,388 controls for follow-up 2). We identified strong evidence of associations between cervical cancer and two new loci: 4q12 (rs13117307, Pcombined, stringently matched=9.69×10(-9), per-allele odds ratio (OR)stringently matched=1.26) and 17q12 (rs8067378, Pcombined, stringently matched=2.00×10(-8), per-allele ORstringently matched=1.18). We additionally replicated an association between HLA-DPB1 and HLA-DPB2 (HLA-DPB1/2) at 6p21.32 and cervical cancer (rs4282438, Pcombined, stringently matched=4.52×10(-27), per-allele ORstringently matched=0.75). Our findings provide new insights into the genetic etiology of cervical cancer.

The distribution of human leucocyte antigen (HLA) allele and haplotype is varied among different ethnic populations. In this study, HLA-A, -B and -DRB1 allele and haplotype frequencies were determined in 8333 volunteer bone marrow donors of Zhejiang Han population using the polymerase chain reaction sequence-based typing. A total of 52 HLA-A, 96 HLA-B and 61 HLA-DRB1 alleles were found. Of these, the top three frequent alleles in HLA-A, HLA-B and HLA-DRB1 loci, respectively, were A*11:01 (24.53%), A*24:02 (17.35%), A*02:01 (11.58%); B*40:01 (15.67%), B*46:01 (11.87%), B*58:01 (9.05%); DRB1*09:01 (17.54%),DRB1*12:02 (9.64%) and DRB1*08:03 (8.65%). A total of 171 A-B-DRB1 haplotypes with a frequency of >0.1% were presented and the five most common haplotypes were A*33:03-B*58:01- DRB1*03:01, A*02:07-B*46:01-DRB1*09:01, A*30:01-B*13:02-DRB1*07:01, A*33:03-B*58:01-RB1*13:02 and A*11:01-B*15:02-DRB1*12:02. The information will be useful for selecting unrelated bone marrow donors and for anthropology studies and pharmacogenomics analysis.

The polymorphism of major histocompatibility complex class I chain-related gene B (MICB) and variations in MICB alleles in a variety of populations have been characterized using several genotyping approaches. In the present study, a novel polymerase chain reaction sequence-based typing (PCR-SBT) method was established for the genotyping of MICB exons 2-6, and the allelic frequency of MICB in the Zhejiang Han population was investigated. Among 400 unrelated healthy Han individuals from Zhejiang Province, China, a total of 20 MICB alleles were identified, of which MICB*005:02:01, MICB*002:01:01, and MICB*004:01:01 were the most predominant alleles, with frequencies of 0.57375, 0.1225, and 0.08375, respectively. Nine MICB alleles were detected on only one occasion, giving a frequency of 0.00125. Of the 118 distinct MICB ∼ HLA-B haplotypes identified, 42 showed significant linkage disequilibrium (P < 0.05). Haplotypes MICB*005:02:01 ∼ B*46:01, MICB*005:02:01 ∼ B*40:01, and MICB*008 ∼ B*58:01 were the most common haplotypes, with frequencies of 0.0978, 0.0761, and 0.0616, respectively. Five novel alleles, MICB*005:07, MICB*005:08, MICB*027, MICB*028, and MICB*029 were identified. Compared with the MICB*005:02:01 sequence, a G > A substitution was observed at nucleotide position 210 in MICB*005:07, and a 1,134 T > C substitution in MICB*005:08 and an 862 G > A substitution in MICB*027 were detected. In addition, it appears that MICB*028 probably arose from MICB*004:01:01 with an A to G substitution at position 1,147 in exon 6. MICB*029 had a G > T transversion at nucleotide position 730 in exon 4, compared with that of MICB*002:01:01. On the basis of the new PCR-SBT assay, these observed results demonstrated MICB allelic variations in the Zhejiang Han population.

HLA-A*33:03:11 differs from A*33:03:01 by one nucleotide substitution in exon 3 at position 531 G>A.

HLA-C*08:128 shows a substitution C to T at position 704 when compared to HLA-C*08:01:01.

Compared with HLA-DQB1*03:03:02:01, HLA-DQB1*03:03:08 and DQB1*03:03:13 have 330 G>C and 349 T>C changes, respectively.

The DNA-based method is used widely for HLA genotyping in routine work, but some allele may be dropout in the genotyping procedure. Here, we reported a case with HLA-A allele dropout in the Sanger PCR-SBT test. The initial PCR-SBT method with a commercial agent kit was not characterized, and the result of Luminex technology indicated the dropout as a HLA-A*02 allele. Subsequently, the sequences of exons 2-4 were fully matched with the A*02:07 and A*11:01:01 by allele group-specific primer amplification PCR-SBT. On further analysis, a novel allele A*02:07:07 was identified, which has one nucleotide difference from A*02:07:01 at position 6 C>G of exon 1. According to the sequencing for 5'-UTR to 3'-UTR, the novel single nucleotide polymorphism of exon 1 was contributed to HLA-A locus allele dropout in the sample. Our results indicated multiplatform analysis is necessary when a conclusive HLA type cannot be determined by a single methodology.

HLA-B*27:147 differs from HLA-B*27:04:01 by a single nucleotide substitution at position 523 C>G.